Shanmugam Nirukshan, Baker Max O D G, Ball Sarah R, Steain Megan, Pham Chi L L, Sunde Margaret
Discipline of Pharmacology, School of Medical Sciences, Faculty of Medicine and Health and Sydney Nano, University of Sydney, Sydney, NSW, 2006, Australia.
Infectious Diseases and Immunology, Central Clinical School, Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia.
Biophys Rev. 2019 Jun;11(3):287-302. doi: 10.1007/s12551-019-00526-1. Epub 2019 May 2.
The functional amyloid state of proteins has in recent years garnered much attention for its role in serving crucial and diverse biological roles. Amyloid is a protein fold characterised by fibrillar morphology, binding of the amyloid-specific dyes Thioflavin T and Congo Red, insolubility and underlying cross-β structure. Amyloids were initially characterised as an aberrant protein fold associated with mammalian disease. However, in the last two decades, functional amyloids have been described in almost all biological systems, from viruses, to bacteria and archaea, to humans. Understanding the structure and role of these amyloids elucidates novel and potentially ancient mechanisms of protein function throughout nature. Many of these microbial functional amyloids are utilised by pathogens for invasion and maintenance of infection. As such, they offer novel avenues for therapies. This review examines the structure and mechanism of known microbial functional amyloids, with a particular focus on the pathogenicity conferred by the production of these structures and the strategies utilised by microbes to interfere with host amyloid structures. The biological importance of microbial amyloid assemblies is highlighted by their ubiquity and diverse functionality.
近年来,蛋白质的功能性淀粉样状态因其在发挥关键且多样的生物学作用中所扮演的角色而备受关注。淀粉样蛋白是一种蛋白质折叠形式,其特征为纤维状形态、与淀粉样特异性染料硫黄素T和刚果红结合、不溶性以及潜在的交叉β结构。淀粉样蛋白最初被描述为与哺乳动物疾病相关的异常蛋白质折叠形式。然而,在过去二十年中,几乎在所有生物系统中都发现了功能性淀粉样蛋白,从病毒到细菌、古菌,再到人类。了解这些淀粉样蛋白的结构和作用有助于阐明自然界中蛋白质功能的新的、可能古老的机制。许多这些微生物功能性淀粉样蛋白被病原体用于入侵和维持感染。因此,它们为治疗提供了新途径。本综述研究了已知微生物功能性淀粉样蛋白的结构和机制,特别关注这些结构的产生所赋予的致病性以及微生物用于干扰宿主淀粉样蛋白结构的策略。微生物淀粉样蛋白组装体的普遍存在和多样功能突出了它们的生物学重要性。